title: Phase II trial to assess the safety and efficacy of clofarabine in combination with low-dose cytarabine in elderly patients with acute myeloid leukemia.
abstract: Previous studies have shown that clofarabine plus low-dose cytarabine (LDAC) could induce roughly 60 % of complete remissions (CR) with acceptable toxicity and induction mortality in elderly acute myeloid leukemia (AML) patients not suitable for intensive chemotherapy. The Programa Español de Tratamientos en Hematología group conducted a trial for patients diagnosed with untreated AML aged 60 years and older, using the combination of clofarabine (20 mg/m(2) × 5 days) plus low-dose cytarabine (20 mg/m(2) × 14 days). The protocol was flexible regarding the use of antifungal and antibacterial prophylaxis, and outpatient induction therapy was allowed. Although the planned recruitment goal was 75 patients, only 11 patients were enrolled (median age, 74 years) after observing high toxicity and unacceptable mortality (46 and 73 % at 4 and 8 weeks, respectively). The response assessment showed three CR (27 %), three resistant diseases (27 %), and five induction deaths (46 %). Induction was administered in an outpatient modality in five patients, while antifungal and antibacterial prophylaxis was not given in seven and five patients, respectively. In our context, induction therapy with the combination of clofarabine (20 mg/m(2)) plus LDAC was associated with high toxicity and unacceptable mortality in elderly AML patients, leading to the early interruption of the trial. Tight patients' clinical monitoring, follow-up, and intensive supportive care seem crucial to achieve at least acceptable clinical outcomes in elderly AML patients receiving clofarabine plus LDAC. This trial is registered at www.clinicaltrials.gov as no. NCT01193400.
authors.affiliation: Hematology Department, Hospital Universitari i Politècnic La Fe, Bulevar Sur s/n, 46026, Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Martínez-Cuadrón
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Olga
authors.initials: O
authors.lastname: Salamero
authors.forename: Belén
authors.initials: B
authors.lastname: Vidriales
authors.forename: Juan
authors.initials: J
authors.lastname: Bergua
authors.forename: Pilar
authors.initials: P
authors.lastname: Herrera
authors.forename: Susanna
authors.initials: S
authors.lastname: Vives
authors.forename: Jaime
authors.initials: J
authors.lastname: Sanz
authors.forename: Cecilia
authors.initials: C
authors.lastname: Carpio
authors.forename: Rebeca
authors.initials: R
authors.lastname: Rodríguez-Veiga
authors.forename: Federico
authors.initials: F
authors.lastname: Moscardó
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects; D000077866:Clofarabine; D015897:Comorbidity; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D017093:Liver Failure / Q000139:chemically induced; D008297:Male; D052016:Mucositis / Q000139:chemically induced; D011446:Prospective Studies; D012074:Remission Induction
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine